Nuclear magnetic resonance spectroscopy, or NMR, is one of the most powerful and commonly used methods for the analysis and elucidation of the chemical structure of molecules. However, NMR suffers from an inherently low sensitivity. This low sensitivity is of particular concern when examining small sample volumes (&lt;1 ml), where the dependence of the NMR signal strength on sample volume results in an enormous reduction in the signal-to-noise ratio (SNR). A poor SNR is a fundamental limitation of NMR microspectroscopy. Conventional NMR spectrometers use radio frequency coils ranging from several millimeters to tens of centimeters in diameter to tightly couple to sample volumes that range from several microliters to greater than 1 liter. In addition, NMR spectroscopy requires that the high strength static magnetic field (B.sub.0) into which the sample is immersed be highly homogeneous (&lt;1 ppm over then entire volume of the sample) and necessitates the use of physically large, highly sophisticated, expensive superconducting magnets. Although recent advancements in high-field magnet technology have provided higher strength magnetic fields with improved homogeneity, the costly purchase price of these large magnets has precluded the development of customized NMR systems.
The radiofrequency (RF) coil used to receive the free-induction decay signal from the sample is a key component of the NMR spectrometer and has a profound effect on the observed SNR. In general, the RF coil can be used both to transmit energy to the sample thereby exciting the sample from its equilibrium state to its excited state, and to receive energy from the sample as it relaxes from its excited state to its equilibrium state. To optimize the detection efficiency, high performance coils with low resistivity and high inductance are designed to tightly couple to the sample and to present a highly homogeneous RF magnetic field to the sample. Although the vast majority of conventional NMR spectrometers use relatively large RF coils (mm to cm size) and samples in the .mu.l to ml volume range, there are significant performance advantages achieved by using smaller size coils when examining very small samples.
Unlike larger systems, where the dominant source of noise is the conducting sample, the primary noise in NMR spectroscopy of small samples is the thermal noise (also called the Johnson noise) of the RF coil. For example, when considering samples with conductivities similar to that of biological tissue (i.e., saline) and static magnetic field strengths of several Tesla, the transition from sample dominated noise to coil dominated noise occurs at a size scale of several millimeters. As the detection sensitivity of the RF coil increases inversely with coil diameter and the variation in coil resistance with coil size is less pronounced, the mass (detection) sensitivity of the system is enhanced at smaller dimensions. This has been the justification of several studies using microcoils to examine mass-limited or volume-limited samples. However, in all previous work, these coils have been used in conventional (large) NMR magnets and with conventional NMR spectrometers, and thus one of the most significant advantages of microcoils has not been realized.